Coro1a-KO Mouse

Coro1a, short for Coronin 1A, is an actin-binding protein that plays crucial roles in multiple biological processes. It is involved in cytoskeleton remodeling, which is essential for processes like receptor-mediated endocytosis, neuronal morphogenesis, and the regulation of autophagy [1,2,4]. It participates in pathways related to steroidogenesis, neuronal development, and autophagic flux, highlighting its overall biological importance. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions.

In Cd-exposed Leydig cells, up-regulation of Coro1a leads to F-actin disassembly, reducing LDL uptake, total cholesterol, and progesterone production. Silencing Coro1a in Cd-treated R2C cells rescues these phenotypes, indicating its role in Cd-induced steroid hormone deficiency [1]. In neuronal morphogenesis, loss of Coro1a leads to similar phenotypes as loss of TRIM67, and a Coro1a mutant unable to bind TRIM67 cannot rescue the loss-of-function phenotypes, suggesting their collaborative role in netrin-dependent neuronal morphogenesis [2]. In triple-negative breast cancer (TNBC), promoting the neddylation-mediated degradation of Coro1a via TRIM4 using a molecular glue (Aurovertin B) inhibits various cellular processes and exerts antitumor effects [3]. In hepatocytes, CREBH inhibits Coro1a expression, and overexpression of Coro1a in LO2 liver cells inhibits autophagic flux and elevates inflammatory cytokine levels [4].

In summary, Coro1a is essential for cytoskeleton-related functions in processes like steroidogenesis, neuronal development, and autophagy. Studies using KO/CKO mouse models (or equivalent loss-of-function experiments) have revealed its significant contributions to diseases such as Cd-induced steroid hormone deficiency, TNBC, and non-alcoholic steatohepatitis (NASH), providing insights into potential therapeutic targets.

References:

1. Wang, Youjin, Li, Teng, Li, Haoji, Huang, Yadong, Zhang, Qihao. 2022. CORO1A regulates lipoprotein uptake in Leydig cells exposed to cadmium. In Ecotoxicology and environmental safety, 232, 113255. doi:10.1016/j.ecoenv.2022.113255. https://pubmed.ncbi.nlm.nih.gov/35121256/

2. Ho, Chris T, Evans, Elliot B, Lukasik, Kimberly, Bear, James E, Gupton, Stephanie L. 2025. Coro1A and TRIM67 collaborate in netrin-dependent neuronal morphogenesis. In bioRxiv : the preprint server for biology, , . doi:10.1101/2025.03.20.644333. https://pubmed.ncbi.nlm.nih.gov/40166342/

3. Gu, Wen-Jie, Liu, Xiao-Xia, Shen, Yi-Wen, Jin, Jin-Mei, Luan, Xin. 2024. TRIM4 enhances small-molecule-induced neddylated-degradation of CORO1A for triple negative breast cancer therapy. In Theranostics, 14, 7023-7041. doi:10.7150/thno.97662. https://pubmed.ncbi.nlm.nih.gov/39629122/

4. Deng, Xiaoling, Liu, Beibei, Jiang, Qianqian, Li, Jiahuan, Xu, Keshu. 2023. CREBH promotes autophagy to ameliorate NASH by regulating Coro1a. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 166914. doi:10.1016/j.bbadis.2023.166914. https://pubmed.ncbi.nlm.nih.gov/37837948/